Welcome

Welcome to the POZ/AIDSmeds Community Forums, a round-the-clock discussion area for people with HIV/AIDS, their friends/family/caregivers, and
others concerned about HIV/AIDS. Click on the links below to browse our various forums; scroll down for a glance at the most recent posts; or join in the
conversation yourself by registering on the left side of this page.

Privacy Warning: Please realize that these forums are open to all, and are fully searchable via Google and other search engines. If you are HIV positive
and disclose this in our forums, then it is almost the same thing as telling the whole world (or at least the World Wide Web). If this concerns you, then do not use a
username or avatar that are self-identifying in any way. We do not allow the deletion of anything you post in these forums, so think before you post.

The information shared in these forums, by moderators and members, is designed to complement, not replace, the relationship between an individual and his/her own
physician.

All members of these forums are, by default, not considered to be licensed medical providers. If otherwise, users must clearly define themselves as such.

Forums members must behave at all times with respect and honesty. Posting guidelines, including time-out and banning policies, have been established by the moderators
of these forums. Click here for “Am I Infected?” posting guidelines. Click here for posting guidelines pertaining to all other POZ/AIDSmeds community forums.

We ask all forums members to provide references for health/medical/scientific information they provide, when it is not a personal experience being discussed. Please
provide hyperlinks with full URLs or full citations of published works not available via the Internet. Additionally, all forums members must post information which are
true and correct to their knowledge.

Approximately 10% of patients taking the antiretroviral drug raltegravir (Isentress) develop central nervous system (CNS) side-effects, research published in the online edition of AIDS shows. The development of CNS side-effects was associated with the co-administration of tenofovir (Viread, also in Truvada, Atripla and Eviplera) and of proton pump inhibitors (drugs used to reduce gastric acid). The investigators believe these drugs interact with raltegravir, increasing its plasma concentrations.

Raltegravir is the only integrase inhibitor so far approved for the treatment of HIV. Clinical trials conducted during the development of raltegravir showed that the drug had a good safety profile. However, some people developed CNS symptoms and there have been case reports of worsening depression and the development of insomnia in people initiating raltegravir therapy.

Italian investigators therefore looked at the prevalence of and risk factors for CNS side-effects in people taking raltegravir in routine HIV care.

Their study sample included 453 raltegravir-treated participants. They were monitored at six-monthly intervals, when they were asked if they had developed CNS symptoms such as headache, dizziness, anxiety, depression and sleep disturbances.

Two-thirds of the participants were men and their median age was 46 years. The mean CD4 cell count was 378 cells/mm3 and mean viral load was 1250 copies/ml. The participants were followed for a median of 23 months.

During this time, 47 individuals (10%) developed at least one drug-related CNS side-effect.

Four people stopped taking their therapy because of CNS symptoms.

There was evidence that the risk of CNS symptoms was increased by certain drug interactions.

Symptoms developed in 14% of participants who were taking the anti-HIV drug tenofovir, compared to 7% of those who were taking an alternative antiretroviral (p = 0.03). CNS symptoms were observed in 26% of people taking a proton pump inhibitor, compared to 9% of individuals who were not taking this type of therapy (p = 0.006).

After controlling for potential confounders, the investigators found that concomitant treatment with tenofovir almost doubled the risk of CNS symptoms (OR = 1.9; 95% CI, 1.0-3.5, p =0.04), whereas treatment with a proton pump inhibitor was associated with a more than three-fold increase in the risk of these symptoms (OR = 3.4; 95% CI, 1.3-8.8, p = 0.01).

The authors draw attention to the results of pharmacokinetic studies that showed that tenofovir can increase plasma levels of raltegravir by up to 64%, and that proton pump inhibitors can increase raltegravir levels by up to 415%.

They recommend “a careful evaluation of patients with psychiatric disease prior to starting raltegravir and a continuous monitoring of CNS symptoms in clinical practice in those starting the drug”. The authors also stress the need to check for drug interactions than could lead to an increase in raltegravir levels. Therapeutic drug level monitoring could be useful, they suggest, for people experiencing CNS symptoms.

“Further prospective studies are needed to better clarify risk factors, the role of drug-interactions and the clinical significance of CNS symptoms in patients receiving raltegravir,” conclude the researchers.

Hey Miss P, I decided to move this thread into the Treatment forum as it's not getting many reads in the Research forum. A lot of people are on Isentress and they'd be more likely to go into the Treatment forum for information like this, rather than the Research forum.

"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts

Another case of science that is not news but gets written up by science writers as news. The 10% rate is similar to the rate seen in the Phase 3 studies for raltegravir. This said, I do find the tenofovir interaction an interesting pointer.

Importantly, the reported discontinuation rate for CNS side effects was around 1% - so much better than efavirenz, but perhaps also sommat to consider here: how many of the people needed to stay on raltegravir because of resistance?

Miss P,Thanks for the article it was a good read. I am not having any problems as of yet but I will pass a copy of this to my IDS. Since he is at a research hospital his department tends to focus on what is relevant to their experiences.Billy

"...health will finally be seen not as a blessing to be wished for, but as a human right to be fought for." Kofi Annan

Nymphomaniac: a woman as obsessed with sex as an average man. Mignon McLaughlin

HIV is certainly character-building. It's made me see all of the shallow things we cling to, like ego and vanity. Of course, I'd rather have a few more T-cells and a little less character. Randy Shilts